Recent insights into NF-κB signalling pathways and the link between inflammation and prostate cancer

Abstract

Inflammation is involved in regulation of cellular events in prostate carcinogenesis through control of the tumour micro-environment. A variety of bone marrow-derived cells, including CD4+ lymphocytes, macrophages and myeloid-derived suppressor cells, are integral components of the tumour micro-environment. On activation by inflammatory cytokines, NF-κB complexes are capable of promoting tumour cell survival through anti-apoptotic signalling in prostate cancer (PCa). Positive feedback loops are able to maintain NF-κB activation. NF-κB activation is also associated with the metastatic phenotype and PCa progression to castration-resistant prostate cancer (CRPC). A novel role for inhibitor of NF-κB kinase (IKK)-α in NF-κB-independent PCa progression to metastasis and CRPC has recently been uncovered, providing a new mechanistic link between inflammation and PCa. Expansion of PCa progenitors by IKK-α may be involved in this process. In this review, we offer the latest evidence regarding the role of the NF-κB pathway in PCa and discuss therapeutic attempts to target the NF-κB pathways. We point out the need to further dissect inflammatory pathways in PCa in order to develop appropriate preventive measures and design novel therapeutic strategies.

Keywords: IKK-α; NF-κB; apoptosis; castration-resistant; inflammation; metastasis; prostate cancer.